The incidence of cancer is increasing worldwide, in spite of substantial progress in the development of anticancer therapies. One approach to control cancer could be its prevention by diet, which inhibit one or more neoplastic events and reduce the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat diabetes and associated complications. It is noteworthy to mention that bitter melon extract has no major side effects in animals as well as in humans. We have recently discovered an anti-proliferative effect of bitter melon extract in a number of cancer cell lines including prostate without affecting the normal cell growth. Treatment of prostate cancer cells with bitter melon extract modulated Bax expression and induced PARP cleavage. Based on our preliminary results, we hypothesize that bitter melon extract may have chemopreventive activity against cancer. To test our hypothesis, we will use prostate cancer as a preclinical model. Aim 1 will evaluate chemopreventive potential of BME against prostate cancer using animal models, and Aim 2 will determine the molecular targets of bitter melon extract for inhibition of human prostate cancer. The results from our proposed study will elucidate the proof-of-concept for prevention or delay of prostate cancer using bitter melon extract, and will have a high potential for translational research. The results from our study will also provide a foundation for future studies for identification of active bitter melon constituent(s) inhibiting prostate cancer. PUBLIC HEALTH RELEVANCE: Prostate cancer is the second leading cause of cancer death in men. Our proposed study will establish the role of bitter melon as a dietary product for prostate cancer prevention in experimental animal models, which will eventually be translated into clinical trial.